Plasma to egg conversion factor for evaluating polychlorinated biphenyl and DDT exposures in great horned owls and bald eagles.

The benefits of nondestructive sampling techniques, such as plasma sampling, to directly measure contaminant exposure levels in at-risk or protected raptor populations are many. However, such assays are generally inconsistent with the most certain source of toxicity reference values, which are based on feeding studies and quantified as dietary or "in ovo" (egg-based) concentrations. An accurate conversion factor to translate nondestructive plasma-based contaminant concentrations to comparable egg-based concentrations will prove valuable to risk assessors investigating the potential effects of chemical exposures to raptors.

Risk assessment of great horned owls (Bubo virginianus) exposed to polychlorinated biphenyls and DDT along the Kalamazoo River, Michigan, USA.

The great horned owl (GHO; Bubo virginianus) was used in a multiple lines of evidence study of polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyltrichloroethane (DDT) exposures at the Kalamazoo River Superfund Site (KRSS), Kalamazoo, Michigan, USA. The study examined risks from total PCBs, including 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQWorld Health Organization [WHO]-Avian Toxicity Equivalency Factor [TEF]), and total DDTs (sum of DDT, dichlorodiphenyldichloroethylene [DDE], and dichlorodiphenyldichloroethane [DDD]; sigmaDDT) by measuring concentrations in eggs and nestling blood plasma in two regions of the KRSS (upper, lower) and an upstream reference area (RA). An ecological risk assessment compared concentrations of the contaminants of concern (COCs) in eggs or plasma to toxicity reference values.

Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice.

Unlabelled: Acetaminophen (N-acetyl-p-aminophenol [APAP]) is one of the leading causes of acute liver failure, and APAP hepatotoxicity is associated with coagulopathy in humans. We tested the hypothesis that activation of the coagulation system and downstream protease-activated receptor (PAR)-1 signaling contribute to APAP-induced liver injury. Fasted C57BL/J6 mice were treated with either saline or APAP (400 mg/kg intraperitoneally) and were euthanized 0.

Transcriptional regulation of deoxynivalenol-induced IL-8 expression in human monocytes.

The trichothecene mycotoxin deoxynivalenol (DON), commonly present in contaminated grains worldwide, induces expression of the chemokine interleukin (IL)-8 in human monocytes. The purpose of this study was to test the hypothesis that DON modulates transcriptional and posttranscriptional regulation of IL-8 expression in the U937 human monocyte model. When U937 cells were transfected with a wild-type IL-8 promoter luciferase construct (-162/+44 IL-8 LUC) and incubated with DON (1 mug/ml) or the positive control, lipopolysaccharide (LPS) (1 mug/ml), there was a significant increase in luciferase expression.

2,2',4,4'-Tetrachlorobiphenyl upregulates cyclooxygenase-2 in HL-60 cells via p38 mitogen-activated protein kinase and NF-kappaB.

Polychlorinated biphenyls (PCBs) are ubiquitous, persistent environmental contaminants that affect a number of cellular systems, including neutrophils. Among the effects caused by the noncoplanar PCB 2,2',4,4'-tetrachlorobiphenyl (2244-TCB) in granulocytic HL-60 cells are increases in superoxide anion production, activation of phospholipase A(2) with subsequent release of arachidonic acid (AA) and upregulation of the inflammatory gene cyclooxygenase-2 (COX-2). The objective of this study was to determine the signal transduction pathways involved in the upregulation of COX-2 by 2244-TCB.

The "low dose" hypothesis: validity and implications for human risk.

In the late 1990s, a "low dose" hypothesis was proposed based on studies that purported to show that hormonally active environmental agents were causing a variety of effects, mainly reproductive and developmental, at "low doses." The supporters of this hypothesis claim that traditional "high-dose" toxicity studies are not adequate to assess adverse effects from these hormonally active agents in that they do not detect effects that are occurring at "low doses." In addition, it is claimed that these "low dose" effects are occurring at levels comparable to those to which humans are being exposed.

dbZach toxicogenomic information management system.

Quantitative risk assessment and the elucidation of mechanisms of toxicity require innovative computational analysis and infrastructure capable of integrating all levels of biological data organization. Enterprise data management solutions provide the capability to manage and integrate disparate data throughout the source-to-outcome continuum. These capabilities enable software engineers and developers to create and validate software solutions to facilitate the identification of more predictive biomarkers for exposures, molecular responses and toxicity, allowing evaluation of historical assessments and the comparison of data across technologies, species and chemical classes.

T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates viral bronchiolitis.

Exposure to immunosuppressive environmental contaminants is a possible contributing factor to increased occurrence of viral respiratory diseases. The objective of this study was to test the hypothesis that the trichothecene mycotoxin T-2 toxin (T-2), a frequent food contaminant, alters host resistance to lung infection by reovirus, a model respiratory virus. Balb/c mice (4 week old) were treated intraperitoneally with T-2 toxin (1.

Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: hormone production.

To identify and prioritize chemicals that may alter steroidogenesis, an in vitro screening assay based on measuring alterations in hormone production was developed using the H295R human adrenocortical carcinoma cell line. Previous studies indicated that this cell line was useful to screen for effects on gene expression of steroidogenic enzymes. This study extended that work to measure the integrated response on production of testosterone (T), estradiol (E2), and progesterone/pregnenolone (P) using an ELISA.

The H295R system for evaluation of endocrine-disrupting effects.

The present studies were undertaken to evaluate the utility of the H295R system as an in vitro assay to assess the potential of chemicals to modulate steroidogenesis. The effects of four model chemicals on the expression of ten steroidogenic genes and on the production of three steroid hormones were examined. Exposures with individual model chemicals as well as binary mixtures were conducted.

Suppression of aromatase activity in populations of bream (Abramis brama) from the river Elbe, Germany.

Aromatase activity was determined in brain and gonads of wild bream collected along the river Elbe, Germany, and correlated with other endocrine and reproductive endpoints such as plasma sex steroid concentrations, secondary sex characteristics (STI), plasma vitellogenin, gonad size (GSI), and maturation stages of germ cells (MS) that were reported for the same fish in a previous study. Furthermore, regional patterns of aromatase activity were correlated to a number of environmental factors such as exposure to environmental contaminants and parasitism. While aromatase activity was not detectable in the gonads of male and female fish with the assay used, fish of both genders revealed relatively great brain enzyme activities.

Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain.

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, the "black mold" suggested to contribute etiologically to illnesses associated with water-damaged buildings. Using an intranasal instillation model in mice, we found that acute SG exposure specifically induced apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium. Dose-response analysis revealed that the no-effect and lowest-effect levels at 24 hr postinstillation (PI) were 5 and 25 microg/kg body weight (bw) SG, respectively, with severity increasing with dose.

Anticoagulation and inhibition of nitric oxide synthase influence hepatic hypoxia after monocrotaline exposure.

Monocrotaline (MCT) is a pyrrolizidine alkaloid plant toxin that produces hepatotoxicity in humans and animals. Administration of MCT to rats causes rapid sinusoidal endothelial cell (SEC) injury, hemorrhage, pooling of blood and fibrin deposition in centrilobular regions of liver. These events precede hepatic parenchymal cell (HPC) injury and produce marked changes in the microvasculature of the liver, which could interrupt blood flow and produce hypoxia in affected regions.

Deoxynivalenol and satratoxin G potentiate proinflammatory cytokine and macrophage inhibitory protein 2 induction by Listeria and Salmonella in the macrophage.

Health risks from microbial pathogens and toxins encountered in food and the environment continue to be of worldwide concern. The purpose of this research was to test the hypothesis that trichothecene mycotoxins amplify inflammatory responses to foodborne bacterial pathogens. We assessed the capacity of deoxynivalenol (DON) and satratoxin G (SG) to potentiate chemokine and proinflammatory cytokine production in RAW 264.

Modeling inflammation-drug interactions in vitro: a rat Kupffer cell-hepatocyte coculture system.

Xenobiotic-inflammation interactions lead to hepatotoxicity in vivo. Selected xenobiotic agents (acetaminophen, APAP; chlorpromazine, CPZ; allyl alcohol, AlOH; monocrotaline, MCT) for which this occurs were evaluated for ability to elicit the release of Kupffer cell (KC)-derived inflammatory mediators and to modulate lipopolysaccharide (LPS)-stimulated release of these mediators. Using KCs and hepatocytes (HPCs) isolated from rat, KC/HPC cocultures were treated with either LPS, xenobiotic, vehicle or a combination.

Accumulation of polychlorinated biphenyls from floodplain soils by passerine birds.

Eggs, nestlings, and adults of the eastern bluebird (Sialia sialis) and house wren (Troglodytes aedon) were collected at a polychlorinated biphenyl (PCB)-contaminated site and a reference location on the Kalamazoo River (MI, USA). Eggs and nestlings of eastern bluebirds at the more contaminated location contained concentrations of 8.3 and 1.

Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants.

Activation of the innate immune system might predispose a host to toxicant-induced inflammation. In vitro macrophage models were employed to investigate the effects of preexposure to Toll-like receptor (TLR) agonists on induction of proinflammatory cytokine gene expression by the trichothecene mycotoxin deoxynivalenol (DON) and other toxicants. Priming of the murine RAW 264.

Induction of cytochrome P4501A in African brown house snake (Lamprophis fuliginosus) primary hepatocytes.

Although there have been numerous studies involving fish, birds, and mammals, little is known about the response of the cytochrome P4501A system of snakes to halogenated aromatic hydrocarbons (HAHs). The present study describes the induction of ethoxyresorufin-O-deethylase (EROD) in primary hepatocytes of the African brown house snake (Lamprophis fuliginosus). Hepatocytes were exposed in multiwell plates to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and four different non-ortho-substituted coplanar polychlorinated biphenyls (PCBs 77, 81, 126, and 169).

Tree swallow (Tachycineta bicolor) exposure to polychlorinated biphenyls at the Kalamazoo River superfund site, Michigan, USA.

In 1990, a portion of the Kalamazoo River in Michigan, USA, was designated a Superfund site because of the presence of polychlorinated biphenyls (PCBs) in the sediment and floodplain soils. During a four-year period from 2000 to 2003, several avian species were monitored for reproductive effects and concentrations of PCBs in tissues attributed to food chain transfer from contaminated sediments. The tree swallow (Tachycineta bicolor) was chosen as a model receptor for contamination of passerine species.

Development and optimization of a Q-RT PCR method to quantify CYP19 mRNA expression in testis of male adult Xenopus laevis: comparisons with aromatase enzyme activity.

Due to limitations of the currently used enzymatic assays, it is difficult to determine aromatase activity in testicular tissue of amphibians. Quantitative reverse transcription polymerase chain reaction (Q-RT PCR) is a sensitive and reliable technique to detect low amounts of mRNA for specific genes. This study was designed to develop and optimize a SYBR Green I-based Q-RT PCR method to quantify CYP19 mRNA in testicular tissue from male Xenopus laevis.

Productivity of tree swallows (Tachycineta bicolor) exposed to PCBs at the Kalamazoo River superfund site.

A 123-km stretch of the Kalamazoo River in Michigan, was designated a Superfund site in 1990 due to historical releases of effluent containing polychlorinated biphenyl (PCB)-contaminated paper waste. Risk to bird species in the river ecosystem was evaluated using the tree swallow (Tachycineta bicolor) as a monitor for possible effects due to PCB exposure at two nesting locations, one in the Superfund site and one in an upstream reference location that is less contaminated with PCBs. In 2 of the 3 years of the study, clutch size at the contaminated location was 3.

Cannabinoid-mediated elevation of intracellular calcium: a structure-activity relationship.

This laboratory has reported previously that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabinol (CBN) robustly elevate intracellular calcium ([Ca(2+)](i)) in resting human and murine T cells, whereas CP55,940 [5-(1,1-dimethylheptyl)-2-(5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)phenol], a high-affinity ligand for CB1 and CB2, does not. In light of our previous studies, the objective of the present investigation was to examine the ability of various cannabinoid compounds to elevate [Ca(2+)](i) in the CB2 receptor-expressing human peripheral blood acute lymphoid leukemia T cell line and the dependence of structural similarity to Delta(9)-THC therein. The present studies demonstrate that CBN and HU-210 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol], both tricyclic and in that respect structurally similar to Delta(9)-THC, elevate [Ca(2+)](i).

Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1 activation and IL-6 gene transcription in mouse macrophages.

The mycotoxin deoxynivalenol (DON) induces IgA nephropathy in mice by upregulating IL-6 expression, which is suppressed by (n-3) PUFA consumption. The purpose of this study was to test the hypothesis that consumption of the (n-3) PUFA docosahexaenoic acid (DHA) interferes with DON-induced transcriptional and post-transcriptional upregulation of IL-6 mRNA in murine macrophages. DON evoked expression of IL-6 mRNA and IL-6 heterogenous nuclear RNA (hnRNA), an indicator of ongoing IL-6 transcription, in macrophages elicited from mice fed control AIN-93G diet for 4 wk, whereas expression of both RNA species was suppressed in macrophages from mice fed AIN-93G modified to contain 30 g DHA/kg diet for the same time period.

Unique gene expression and hepatocellular injury in the lipopolysaccharide-ranitidine drug idiosyncrasy rat model: comparison with famotidine.

Rats cotreated with lipopolysaccharide (LPS) and ranitidine (RAN) but not LPS and famotidine (FAM) develop hepatocellular injury in an animal model of idiosyncratic drug reactions. Evaluation of liver gene expression in rats given LPS and/or RAN led to confirmation that the hemostatic system, hypoxia, and neutrophils (PMNs) are critical mediators in LPS/RAN-induced liver injury. We tested the hypothesis that unique gene expression changes distinguish LPS/RAN-treated rats from rats given LPS or RAN alone and from those cotreated with LPS/FAM.

Coagulation-dependent gene expression and liver injury in rats given lipopolysaccharide with ranitidine but not with famotidine.

In an animal model of drug idiosyncrasy, rats cotreated with nonhepatotoxic doses of lipopolysaccharide (LPS) and ranitidine (RAN) develop hepatocellular injury, whereas rats treated with LPS and famotidine (FAM) do not. The coagulation system and neutrophils (PMNs) are requisite mediators of LPS/RAN-induced liver injury. We tested the hypothesis that unique gene expression in LPS/RAN-treated rats requires coagulation system activation and that these changes are absent in rats given LPS and FAM.